Mechanical stretch induces nerve sprouting in rat sympathetic neurocytes

Auton Neurosci. 2010 Jun 24;155(1-2):25-32. doi: 10.1016/j.autneu.2010.01.003. Epub 2010 Feb 1.

Abstract

Sympathetic nerve sprouting (SNS) has been shown to occur after myocardial infarction (MI) and heart failure (HF) and is known to be responsible for the development of lethal arrhythmias. During MI or HF intracardiac cells are exposed to increased mechanical stretch. Molecular mechanisms which trigger sympathetic neural growth are largely unknown. Therefore, this study aimed to investigate the impact of mechanical stretch on rat neonatal sympathetic neurocytes of the superior cervical ganglion (SCG). Mechanical stretch resulted in an increased growth of sympathetic neurocytes. Furthermore, we could demonstrate that SCG neurocytes express nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), neurotrophin-3 (NT-3) and glial derived neurotrophic factor (GDNF) on mRNA and protein level. An increased NGF and CNTF expression, a down-regulated GDNF expression and an unchanged NT-3 expression were identified in the neurocyte cell culture supernatant of neurocytes exposed to mechanical stretch. However, neither brain derived neurotrophic factor (BDNF) mRNA and protein was expressed in SCG neurocytes, nor BDNF could be detected in the cell culture supernatant of SCG neurons. By anti-neurotrophin neutralizing experiments NGF and CNTF were identified as important stretch-induced growth-inducing factors. Losartan, an angiotensin-II type 1 receptor inhibitor, abolished the stretch-induced increase of NGF and CNTF expression and thereby prevented the stretch-induced neural growth. This study provides new molecular mechanisms by which the inhibitory effect of angiotensin-II type 1 receptor blockers on the neural/arrhythmogenic remodeling can be explained. However, further in-vivo studies are required to address this important issue.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Blotting, Western
  • Cell Enlargement* / drug effects
  • Cells, Cultured
  • Ciliary Neurotrophic Factor / biosynthesis
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Glial Cell Line-Derived Neurotrophic Factor / biosynthesis
  • Losartan / pharmacology
  • Mechanotransduction, Cellular / drug effects
  • Mechanotransduction, Cellular / physiology*
  • Nerve Growth Factor / biosynthesis*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Polysaccharides / biosynthesis
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stress, Mechanical
  • Superior Cervical Ganglion / drug effects
  • Superior Cervical Ganglion / metabolism*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Ciliary Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor
  • Polysaccharides
  • RNA, Messenger
  • neurotropin
  • Nerve Growth Factor
  • Losartan